Dual HER2-blockade shows anti-tumour activity in patients with uterine cancer

In the phase 2 TAPUR basket trial, the combination of pertuzumab and trastuzumab demonstrated anti-tumour activity in heavily pre-treated patients with uterine cancer with HER2 amplification and/or specific mutations. Additional study is warranted to confirm the efficacy of pertuzumab and trastuzumab in this patient population.

Unlike in breast cancer, the clinical significance of HER2 gene amplification in uterine cancer is controversial since the single-agent trastuzumab has shown little activity in HER2-positive endometrial cancer. TAPUR is a phase 2 basket study (NCT02693535) evaluating the anti-tumour activity of commercially available targeted agents in patients with advanced solid cancers harbouring genomic alterations known to be drug targets. The primary endpoint of TAPUR is disease control, defined as objective response, or stable disease for at least 16 weeks. Dr Eugene Ahn (Cancer Treatment Centers of America, IL, USA) presented results from the uterine cancer cohort of TAPUR [1].

Enrolled were 28 heavily pretreated patients with advanced uterine cancer with HER2 or HER3 amplification or overexpression or a pre-specified HER2 mutation. Eligible participants had no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. They were treated with pertuzumab and trastuzumab (every 3 weeks) until disease progression.

The disease control rate was 37%, and the objective response rate was 7%. At 16 weeks, 2 patients had a partial response, and 8 patients achieved stable disease. Median progression-free survival was 28.1 weeks; median overall survival was 60.9 weeks. One patient experienced grade 3 muscle weakness, which was at least possibly related to pertuzumab/trastuzumab.

1. Hussein MA, et al. Pertuzumab plus trastuzumab (P+T) in patients (Pts) with uterine cancer (UC) with ERBB2 or ERBB3 amplification, overexpression or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. Abstract 5508, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202129 February, 2024